We have shown that the exposure of normal human platelets to either ADP or thrombin brings about profound changes in the composition of the glycosphingolipids of these cells, most remarkable of which is the increase in the level of GM3 ganglioside (hematoside) during aggregation. We now propose to study this phenomenon in detail, since it is possible that the regulation of sociological behavior of cells (cellular adhesion, for example) is mediated by sialoglycosphingolipids and/or sialoglycoproteins. The levels of cell surface glycosphingolipids and glycoproteins of normal platelets will be determined before and after aggregation and deaggregation, and comparisons of the results will be made with those using platelets from patients with clinical abnormalities such as alcoholic cirrhosis, acute refractory anemia and Type IV hyperlipemia. The role of ceramide and lactosylceramide in hematoside biosynthesis will be evaluated, especially with regard to the possibility that a glycosyl transferase is actually activated during aggregation; it may even be an early step in the initiation of aggregation. An alternative mechanism leading to concentration changes of platelet glycosphingolipids, involving exchange with plasma or erythrocyte pools of these lipids, will also be investigated. If the biochemical transformations of some of the glycosphingolipids are found to be important in aggregation, specific abnormalities may be discovered in some of the clinical disorders characterized by bleeding, an understanding of which could lead to rational proposals for experimental therapy.